Male genes: X‐pelled or X‐cluded?

Two recent studies by Parisi et al. and Ranz et al., catalogue sex differences in gene expression across the whole genome of the fruit fly Drosophila melanogaster. Both report striking associations of sex-biased gene expression with the X chromosome. Genes with male-biased expression are depauperate on the X chromosome, whereas genes with female-biased expression show weaker evidence of being in excess. A number of evolutionary hypotheses for the expulsion or exclusion of male-biased genes from the X chromosome have been suggested. None is entirely consistent with the available evidence.     

The α‐sheet: A missing‐in‐action secondary structure?

The α-sheet has been speculated to play a role as a toxic conformer in amyloid diseases. However, except for relatively short fragments, its detection has remained elusive. Here, we present molecular dynamics simulations that support the existence of the α-sheet as a stable, metastable, or long-lived secondary structure in polyglutamine and, to a lesser extent, in polyasparagine aggregates.     

Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

MATHEMATICS OF KIN‐ AND GROUP‐SELECTION: FORMALLY EQUIVALENT?

Evolutionary game theory is a general mathematical framework that describes the evolution of social traits. This framework forms the basis of many multilevel selection models and is also frequently used to model evolutionary dynamics on networks. Kin selection, which was initially restricted to describe social interactions between relatives, has also led to a broader mathematical approach, inclusive fitness, that can not only describe social evolution among relatives, but also in group structured populations or on social networks. It turns out that the underlying mathematics of game theory is fundamentally different from the approach of inclusive fitness. Thus, both approaches—evolutionary game theory and inclusive fitness—can be helpful to understand the evolution of social traits in group structured or spatially extended populations.     

Song and Sperm in Crickets: A Trade‐off between Pre‐ and Post‐copulatory Traits or Phenotype‐Linked Fertility?

When females mate multiply (polyandry) both pre‐ and post‐copulatory sexual selection can occur. Sperm competition theory predicts there should be a trade‐off between investment in attracting mates and investment in ejaculate quality. In contrast, the phenotype‐linked fertility hypothesis predicts a positive relationship should exist between investment in attracting mates and investment in ejaculate quality. Given the need to understand how pre‐ and post‐copulatory sexual selection interacts, we investigated the relationship between secondary sexual traits and ejaculate quality using the European house cricket, Acheta domesticus. Although we found no direct relationship between cricket secondary sexual signals and ejaculate quality, variation in ejaculate quality was dependent on male body weight and mating latency: the lightest males produced twice as many sperm as the heaviest males but took longer to mate with females. Our findings are consistent with current theoretical models of sperm competition. Given light males may have lower mating success than heavy males because females take longer to mate with them in no‐choice tests, light males may be exhibiting an alternative reproductive tactic by providing females with more living sperm. Together, our findings suggest that the fitness of heavy males may depend on pre‐copulatory sexual selection, while the fitness of light males may depend on post‐copulatory fertilization success.     

Unsaturated fatty acid‐induced non‐canonical autophagy: unusual? or unappreciated?

The breakdown of cellular components via autophagy is crucial for cellular homeostasis. In this issue of The EMBO Journal, Niso‐Santano et al ( 2015 ) report the important observation that feeding cells with saturated or unsaturated fatty acids triggers mechanistically distinct autophagic responses. Feeding cells saturated fatty acid induced the canonical, BECN1/PI3K‐dependent autophagy pathway. Conversely, the unsaturated fatty acid oleate triggered autophagic responses that were independent of the BECN1/PI3K complex, but that required a functional Golgi system.     

Phylogeography of a high‐dispersal New Zealand sea‐star: does upwelling block gene‐flow?

New Zealand's (NZ) geographical isolation, extensive coastline and well-characterized oceanography offer a valuable system for marine biogeographical research. Here we use mtDNA control region sequences in the abundant endemic sea-star Patiriella regularis to test the following literature-based predictions: that coastal upwelling disrupts north-south gene flow and promotes population differentiation (hypothesis 1); and that an invasive Tasmanian population of the species was introduced anthropogenically from southern New Zealand (hypothesis 2). We sequenced 114 samples from 22 geographical locations, including nine sites from North Island, nine from South Island, one from Stewart Island and three from Tasmania. Our analysis of these sequences revealed an abundance of shallow phylogenetic lineages within P. regularis (68 haplotypes, mean divergence 0.9%). We detected significant genetic heterogeneity between pooled samples from northern vs. southern New Zealand (FST = 0.072; P = 0.0002), consistent with the hypothesis that upwelling disrupts gene flow between these regions (hypothesis 1). However, we are currently unable to rule out the alternative hypothesis that Cook Strait represents a barrier to dispersal (North Island vs. South Island; FST = 0.031; P = 0.0467). The detection of significant spatial structure in NZ samples is consistent with restricted gene flow, and the strong structure evident in northern NZ may be facilitated by distinct ocean current systems. Four shared haplotypes and nonsignificant differentiation (FST = 0.025; P = 0.2525) between southern New Zealand and Tasmanian samples is consistent with an anthropogenic origin for the latter population (hypothesis 2).     

Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal,an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration?

4-Hydroxy-2,3-trans-nonenal (HNE) is a neurotoxic unsaturated aldehyde end-product of lipid peroxidation. The addition of HNE to NT-2 and SK-N-MC cell lines induces apoptosis and we now investigated the time-course of events occurring prior to apoptosis. Treatment of both NT-2 and SK-N-MC cell lines with HNE led to HNE association with the proteasome, increased levels of protein carbonyls and ubiquitinated proteins, and decreased proteasomal function. There was also decreased metabolic activity, cytochrome c release and activation of caspase 3, followed by apoptotic changes including chromatin condensation, cell shrinkage and DNA fragmentation and laddering. Overexpression of mutant superoxide dismutase 1 proteins associated with amyotrophic lateral sclerosis decreased proteasomal activities in the absence of HNE and accelerated the apoptosis induced by HNE. By contrast, overexpression of wild-type superoxide dismutase 1 did not affect basal levels of proteasomal activity. The data suggest that accumulation of ubiquitinated proteins and impairment of proteasomal function are important events in HNE toxicity. We propose that the proteasomal system is a significant target of HNE neurotoxicity in a wide range of neurodegenerative diseases, especially if abnormal proteins are being expressed.     

Perovskite Solar Cells: Can We Go Organic‐Free,Lead‐Free,and Dopant‐Free?

Having demonstrated incredibly fast progress in power conversion efficiency, rising to a level comparable with that of crystalline silicon cells, lead‐based organic–inorganic hybrid perovskite solar cells are now facing the stability tests needed for industrialization. Poor thermal stability (<150 °C) owing to organic constituents and interlayer diffusion of materials (dopants), and environmental incompatibility due to Pb has surged the development of organic‐free, Pb‐free perovskites and dopant‐free hole transport materials (HTMs). The recent rapid increase in efficiency of cells based on inorganic perovskites, crossing 18%, demonstrates the great potential of inorganic perovskites as thermally stable and high‐efficiency cells. Although all kinds of Pb‐free perovskites lag in efficiency in comparison to the hybrid and inorganic perovskites, they also demonstrate better structural and environmental stability. The performance of dopant‐free HTMs matching/surpassing dopant‐containing HTMs makes the former a better choice for stability. Even though the efforts to enhance the stability of Pb‐based hybrid perovskites should continue by different techniques, organic‐free and lead‐free perovskites, and dopant‐free HTMs must be pursued with greater interest for the future. This review describes the present issues and possible strategies to address them, and thus will help to improve the overall performance of robust organic‐free, Pb‐free, and dopant‐free perovskite solar cells.     

Post‐dispersal seed recovery by animals: is it a plant‐ or an animal‐driven process?

The ability of animals to find and consume hoarded seeds (i.e. seed recovery) is a key stage within the seed dispersal process. However, the ecology of seed recovery is still poorly understood. Here, we analyze the factors controlling seed recovery by scatter‐hoarding rodents in an oak‐dominated temperate forest. We examined the relative importance of intrinsic seed traits (i.e. plant‐driven) and extrinsic seed factors (i.e. animal‐driven) on the probability of seed recovery. We found that seed recovery is mainly driven by extrinsic seed factors, mostly related to animal behavior (pilfering frequency, microsite preference, predation risk, burial depth and cache size). Important intrinsic traits such as seed size, seed quality and seed‐drop timing were, on average, of lower significance in the probability of seed recovery (2.8‐times less important than extrinsic factors); only seed quality was an important intrinsic trait. On the other hand, larger and nutritionally more valuable seeds showed a removal–recovery tradeoff as they enhance seed removal and hoarding (increasing dispersal quality) but also favour seed recovery (increasing predation). We find that other mechanisms beyond seed traits (e.g. masting) are needed to decrease seed recovery and, thus, increase seed survival. We conclude that, as seed recovery is mostly driven by animal behavioural factors, it substantially differs from other previous stages of the seed dispersal process that are more dependent on seed traits. We argue that seed recovery needs further attention to advance our understanding of the ecology of seed dispersal and the role of secondary dispersers as a selective force for seeds.     

The hemolymph proteome of the honeybee: Gel‐based or gel‐free?

The honeybee has an invaluable economic impact and is a model for studying immunity, development and social behavior. The recent sequencing and annotation of the honeybee genome facilitates the study of its hemolymph, which reflects the physiological condition and mediates immune responses. We aimed at making a proteomic reference map of honeybee hemolymph and compared gel‐free and gel‐based techniques. One hundered and four 2‐DE spots corresponding to 62 different proteins were identified. Eight identical 2‐DLC experiments resulted in the identification of 32 unique proteins. One repeat was clearly not representative for the potential of the given 2‐DLC setup. Only 27% of the identified hemolymph proteins were found by both techniques. In addition, we found proteins of three different viruses which creates possibilities for biomarker design. Future hemolymph studies will benefit from this work.     

Genomic‐scale comparison of sequence‐ and structure‐based methods of function prediction: Does structure provide additional insight?

A function annotation method using the sequence-to-structure-to-function paradigm is applied to the identification of all disulfide oxidoreductases in the Saccharomyces cerevisiae genome. The method identifies 27 sequences as potential disulfide oxidoreductases. All previously known thioredoxins, glutaredoxins, and disulfide isomerases are correctly identified. Three of the 27 predictions are probable false-positives. Three novel predictions, which subsequently have been experimentally validated, are presented. Two additional novel predictions suggest a disulfide oxidoreductase regulatory mechanism for two subunits (OST3 and OST6) of the yeast oligosaccharyltransferase complex. Based on homology, this prediction can be extended to a potential tumor suppressor gene, N33, in humans, whose biochemical function was not previously known. Attempts to obtain a folded, active N33 construct to test the prediction were unsuccessful. The results show that structure prediction coupled with biochemically relevant structural motifs is a powerful method for the function annotation of genome sequences and can provide more detailed, robust predictions than function prediction methods that rely on sequence comparison alone.     

The theoretical basis of cancer‐stem‐cell‐based therapeutics of cancer: can it be put into practice?

In spite of the advances in our knowledge of cancer biology, most cancers remain not curable with present therapies. Current treatments consider cancer as resulting from uncontrolled proliferation and are non-specific. Although they can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but recent developments indicate that different types of cells contribute to the tumour structure, and that the tumour's cellular organization would be analogous to that of a normal tissue, with a main mass of differentiating cells sensitive to anti proliferative agents, together with a small percentage of quiescent, resistant stem cells responsible for replenishing the tumour: the Cancer Stem Cells (CSCs). Anti-CSCs targeted therapeutic agents would prevent tumour regeneration. New mouse models tailored to exploit this novel concept will be critical to develop CSC-based anti-cancer therapies. Here we review the biological basis and the therapeutic implications of the stem-cell model of cancer.     

Pisodonophis boro (ophichthidae: anguilliformes): Specialization for head‐first and tail‐first burrowing?

The rice paddy eel, Pisodonophis boro (P. boro), is of special interest because of its peculiar burrowing habits. P. boro penetrates the substrate tail-first, a technique common for ophichthids, but it is able to burrow head-first as well. P. boro exhibits three feeding modes: inertial feeding, grasping, and spinning. Rotational feeding is a highly specialized feeding mode, adopted by several elongate, aquatic vertebrates and it is likely that some morphological modifications are related to this feeding mode. The detailed morphology of the head and tail of P. boro is examined with the goal to apportion the anatomical specializations among head-first burrowing, tail-first burrowing, and rotational feeding. The reduced eyes, covered with thick corneas may be beneficial for protection during head-first burrowing, but at the same time decreased visual acuity may have an impact on other sensory systems (e.g. cephalic lateral line system). The elongated and pointed shape of the skull is beneficial for substrate penetration. The cranial bones and their joints, which are fortified, are advantageous for resisting high mechanical loads during head-first burrowing. The aponeurotic connection between epaxial and jaw muscles is considered beneficial for transferring these forces from the body to the head during rotational feeding. Hypertrophied jaw muscles facilitate a powerful bite, which is required to hold prey during spinning movements and variability in the fiber angles of subdivisions of jaw muscles may be beneficial for preventing the lower jaw from being dislodged or opened. Furthermore, firm upper (premaxillo-ethmovomerine complex) and lower jaws (with robust coronoid processes) and high neurocranial rigidity are advantageous for a solid grip to hold prey during rotational feeding. The pointed shape of the tail and the consolidated caudal skeleton are beneficial for their tail-first burrowing habits. It is quite likely that the reduction of the caudal musculature is related to the tail-first burrowing behavior because the subtle movements of the caudal fin rays are no longer required.     

Étienne Geoffroy St.‐Hilaire: father of “evo‐devo”?

SUMMARY In the early decades of the nineteenth century, the most important disagreement among comparative anatomists was not evolution versus "special creation" but between advocates of "transcendental morphology" and those of teleological anatomy—form versus function. In France this dichotomy was represented by the 1830–1832 public debate between Geoffroy St.-Hilaire (form) and Cuvier (function). Geoffroy's aim was to establish links of homology (known to him as "analogies") between the four "embranchements" into which Cuvier had divided the animal kingdom. Despite the fanciful nature of some of his homologies, Geoffroy, who was guided by his " principe de connections ," set in motion a school of morphology, some of whose conclusions, notably the homology of the dorsal surface of segmented invertebrates with the ventral surface of vertebrates, has been corroborated by recent studies in developmental genetics.     

Passive immunization against oral AIDS virus transmission: An approach to prevent mother‐to‐infant HIV‐1 transmission?

To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.     

Comparison of X‐ray and NMR structures: Is there a systematic difference in residue contacts between X‐ray‐ and NMR‐resolved protein structures?

We have compared structures of 78 proteins determined by both NMR and X-ray methods. It is shown that X-ray and NMR structures of the same protein have more differences than various X-ray structures obtained for the protein, and even more than various NMR structures of the protein. X-ray and NMR structures of 18 of these 78 proteins have obvious large-scale structural differences that seem to reflect a difference of crystal and solution structures. The other 60 pairs of structures have only small-scale differences comparable with differences between various X-ray or various NMR structures of a protein; we have analyzed these structures more attentively. One of the main differences between NMR and X-ray structures concerns the number of contacts per residue: (1) NMR structures presented in PDB have more contacts than X-ray structures at distances below 3.0 A and 4.5-6.5 A, and fewer contacts at distances of 3.0-4.5 A and 6.5-8.0 A; (2) this difference in the number of contacts is greater for internal residues than for external ones, and it is larger for beta-containing proteins than for all-alpha proteins. Another significant difference is that the main-chain hydrogen bonds identified in X-ray and NMR structures often differ. Their correlation is 69% only. However, analogous difference is found for refined and rerefined NMR structures, allowing us to suggest that the observed difference in interresidue contacts of X-ray and NMR structures of the same proteins is due mainly to a difference in mathematical treatment of experimental results.     

Anomalies of the forebrain with radial limb defects: Garcia‐Lurie‐Steinfeld syndrome?

BACKGROUND: Severe anomalies of the forebrain together with radial limb anomalies have been reported in Steinfeld syndrome, XK aprosencephaly, and partial monosomy 13q. Steinfeld syndrome is an extremely variable autosomal dominant condition that, in severe cases, is characterized by holoprosencephaly, radial limb defects, and renal and/or cardiac defects. In mild cases there may be only thumb hypoplasia, ocular coloboma, or oral clefts. XK aprosencephaly, also called Garcia-Lurie syndrome (GLS), is a usually sporadic disorder with radial limb defects and aprosencephaly/atelencephaly. Based on two atypical sibships, autosomal recessive inheritance has been suggested. Two patients with variations of monosomy 13q have been described with atelencephaly but, generally, Steinfeld and XK aprosencephaly patients are chromosomally normal. Holoprosencephaly in 13q deletion patients appears to be due to ZIC2 mutations, but ZIC2 has not been previously tested in Steinfeld syndrome or GLS patients. CASES: We report three sporadic cases with clinical features intermediate between Steinfeld and GLS, including severe forebrain malformations and radial limb defects. All had normal karyotypes, and mutations in ZIC2 were absent in the two cases tested. CONCLUSIONS: In our cases and in the literature there is significant clinical overlap between Steinfeld syndrome and GLS. We propose these conditions may not be nosologically or etiologically distinct. The spectrum of severe forebrain anomalies in these conditions is broader than previously thought and may include some neural tube defects. Mild cases are difficult to identify and the full range of expression remains unknown. Autosomal dominant inheritance with incomplete penetrance and frequent new mutations is postulated. Thorough clinical evaluation is recommended for children with severe forebrain and radial limb defects.